Johns Hopkins Medicine joins the National Cancer Institute in its CTD2 initiative.

Credit: National Cancer Institute

What do math, physics and engineering tell us about breast cancer? They could tell us a lot, say Johns Hopkins scientists. They’re using a $5 million grant from the National Cancer Institute to unite biologists, clinicians and engineers at the new Johns Hopkins Center for Cancer Target Discovery and Development, or CTD2.

Joel S. Bader, Ph.D., professor of biomedical engineering at the Johns Hopkins University Whiting School of Engineering, and Andrew J. Ewald, Ph.D., associate professor of cell biology at the Institute for Basic Biomedical Sciences at the Johns Hopkins University School of Medicine, are joining forces with three Johns Hopkins clinical faculty members — David Euhus, M.D., professor of surgery; Ashley Cimino-Mathews, M.D., associate professor of pathology; and Edward Gabrielson, M.D., professor of pathology; all at the Johns Hopkins University School of Medicine — to identify the genes driving breast cancer growth and metastasis. These traits distinguish deadly breast cancers from others with much higher survival rates. By connecting a tumor’s behavior to its molecular characteristics, they hope to reveal entirely new therapeutic strategies.

“We are taking concepts from applied mathematics and using them in the discovery of new cancer therapy targets in a way that has not been done before,” says Ewald.

Unlike efforts to identify cancer targets by characterizing the average molecular properties of tumors, the CTD2 team will focus on the cells with the most dangerous behaviors, uniting quantitative imaging with concepts from math and physics to assess the behavior of human breast tumor tissues in the lab. This effort relies on organoids, or collections of cells grown in 3-D culture, to mimic the conditions in the body that allow tumors to invade healthy tissue, metastasize, resist therapy and create tumor cell colonies at distant sites. By quantifying how well diverse sets of tumors and organoids perform these behaviors, researchers hope to determine which genetic mutations enable a tumor to metastasize, and then identify new targets for therapeutic intervention.

“Each patient’s tumor is unique and even within a tumor, each cell can have distinct molecular properties,” says Bader. “This heterogeneity is why cancer is difficult to treat. Here, we are using the same heterogeneity as an Achilles’ heel to discover new vulnerabilities and exploit them as targets.”